PMID- 23684388
OWN - NLM
STAT- MEDLINE
DCOM- 20140117
LR  - 20130621
IS  - 1872-7913 (Electronic)
IS  - 0924-8579 (Linking)
VI  - 42
IP  - 1
DP  - 2013 Jul
TI  - Pharmacokinetic/pharmacodynamic evaluation of the efficacy and safety of 
      daptomycin against Staphylococcus aureus.
PG  - 53-8
LID - S0924-8579(13)00069-1 [pii]
LID - 10.1016/j.ijantimicag.2013.02.009 [doi]
AB  - Daptomycin is a novel lipopeptide exhibiting concentration-dependent bactericidal 
      activity against multidrug-resistant Gram-positive pathogens, including MRSA. 
      Approval of daptomycin is granted at 4-6 mg/kg once daily, however off-label use 
      of doses up to 12 mg/kg daily has been utilised without evidence of significant 
      toxicity. Our aim was to optimise daptomycin regimens by assessing the 
      probability of bacteriological efficacy (pTA) and toxicity (pTOX) at various MICs 
      using Monte Carlo simulation (MCS) techniques. Population pharmacokinetic, 
      pharmacodynamic and toxicodynamic models were developed based on current 
      literature. MCS was performed for 10000 patients, who were assigned true weight 
      and creatinine clearances, and were infected with four Staphylococcus aureus 
      strains at each MIC. Bacteriostatic and bactericidal %pTA was calculated 
      following administration of 6, 8, 10 and 12 mg/kg daptomycin; activity was deemed 
      adequate at %pTA >/= 90%. Considerable pharmacodynamic variability was observed in 
      derived AUC/MIC targets between strains. Bacteriostatic targets were adequately 
      attained against all strains at MIC </= 1 mg/L with daptomycin > 6 mg/kg. However, 
      bactericidal target attainment was only achieved against all strains at the 
      lowest MIC of 0.5 mg/L with daptomycin > 8 mg/kg. At MIC = 2 mg/kg, bactericidal 
      target attainment was extremely poor even at the highest dose of 12 mg/kg. pTOX 
      increased from 3.31% to 17.7% following exposure to 6 mg/kg to 12 mg/kg daily, 
      respectively. Formal benefit:risk analyses favoured doses of 10 mg/kg against 
      infections with MIC < 2 mg/L, whilst modest improvements in activity at 12 mg/kg 
      could not justify the marked increase in pTOX.
CI  - Copyright (c) 2013. Published by Elsevier B.V.
FAU - Soon, Rachel L
AU  - Soon RL
AD  - State University of New York at Buffalo, School of Pharmacy and Pharmaceutical 
      Sciences, Buffalo, NY 14214, USA.
FAU - Turner, Stuart J
AU  - Turner SJ
FAU - Forrest, Alan
AU  - Forrest A
FAU - Tsuji, Brian T
AU  - Tsuji BT
FAU - Brown, Jack
AU  - Brown J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130515
PL  - Netherlands
TA  - Int J Antimicrob Agents
JT  - International journal of antimicrobial agents
JID - 9111860
RN  - 0 (Anti-Bacterial Agents)
RN  - NWQ5N31VKK (Daptomycin)
SB  - IM
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacokinetics/*pharmacology
MH  - Daptomycin/administration & dosage/*pharmacokinetics/*pharmacology
MH  - Humans
MH  - Microbial Sensitivity Tests
MH  - Models, Statistical
MH  - Staphylococcal Infections/drug therapy
MH  - Staphylococcus aureus/*drug effects
MH  - Time Factors
EDAT- 2013/05/21 06:00
MHDA- 2014/01/18 06:00
CRDT- 2013/05/21 06:00
PHST- 2012/10/29 00:00 [received]
PHST- 2012/12/03 00:00 [revised]
PHST- 2013/02/11 00:00 [accepted]
PHST- 2013/05/21 06:00 [entrez]
PHST- 2013/05/21 06:00 [pubmed]
PHST- 2014/01/18 06:00 [medline]
AID - S0924-8579(13)00069-1 [pii]
AID - 10.1016/j.ijantimicag.2013.02.009 [doi]
PST - ppublish
SO  - Int J Antimicrob Agents. 2013 Jul;42(1):53-8. doi: 
      10.1016/j.ijantimicag.2013.02.009. Epub 2013 May 15.